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PMID: 20542253 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Coronaviruses Hijack the LC3-I-positive EDEMosomes, ER-derived vesicles exporting short-lived ERAD regulators, for replication.

Cell host & microbe ·Vol. 7 ·No. 6 ·2010-06-25 ·Pages 500-8

Reggiori F, Monastyrska I, Verheije MH, Calì T, Ulasli M, Bianchi S, Bernasconi R, de Haan CA, Molinari M

Abstract

Coronaviruses (CoV), including SARS and mouse hepatitis virus (MHV), are enveloped RNA viruses that induce formation of double-membrane vesicles (DMVs) and target their replication and transcription complexes (RTCs) on the DMV-limiting membranes. The DMV biogenesis has been connected with the early secretory pathway. CoV-induced DMVs, however, lack conventional endoplasmic reticulum (ER) or Golgi protein markers, leaving their membrane origins in question. We show that MHV co-opts the host cell machinery for COPII-independent vesicular ER export of a short-living regulator of ER-associated degradation (ERAD), EDEM1, to derive cellular membranes for replication. MHV infection causes accumulation of EDEM1 and OS-9, another short-living ER chaperone, in the DMVs. DMVs are coated with the nonlipidated LC3/Atg8 autophagy marker. Downregulation of LC3, but not inactivation of host cell autophagy, protects cells from CoV infection. Our study identifies the host cellular pathway hijacked for supplying CoV replication membranes and describes an autophagy-independent role for nonlipidated LC3-I.

MeSH Terms
Animals Cells, Cultured Cytoplasmic Vesicles/chemistry,virology Endoplasmic Reticulum/virology Membrane Proteins/metabolism Microscopy, Confocal Microscopy, Electron, Transmission Microscopy, Fluorescence Microtubule-Associated Proteins/analysis Murine hepatitis virus/physiology Ubiquitins/analysis Virus Replication
Chemicals
Edem1 protein, mouse Gabarapl1 protein, mouse Map1lc3b protein, mouse Membrane Proteins Microtubule-Associated Proteins Ubiquitins
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Reggiori Fulvio
Department of Cell Biology, University Medical Centre Utrecht, 3584 CX Utrecht, The Netherlands. [email protected]
Monastyrska Iryna
Verheije Monique H
Calì Tito
Ulasli Mustafa
Bianchi Siro
Bernasconi Riccardo
de Haan Cornelis A M
Molinari Maurizio
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Article Info
Journal
Cell host & microbe
Abbr.
Cell Host Microbe
ISSN
1934-6069
DOI
10.1016/j.chom.2010.05.013
Email
[email protected]
Published
2010-06-25
Pages
500-8
Language
English
Region
United States
NLM ID
101302316
PMCID
PMC7103375
Subset
IM
Corrections
CommentIn
PMID: 20542246
External Links
PubMed source DOI: 10.1016/j.chom.2010.05.013 PMC Full Text View journal details
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